The major goals of this research are directed toward elucidating the minimum requirements for the stimulation of T cells by Ia-molecules on allogeneic stimulator cells in the mixed lymphocyte reaction (MLR). We wish to specifically address the question of why certain Ia-positive cell types are capable of stimulating a MLR whereas others are not. Our investigations will focus on cells of the B lymphocyte lineage. The specific aims to achieve these goals are as follows: (1)\To evaluate B cells at various stages of activation and B cell tumors for their capacity to present allo-Ia-determinants for a MLR. (2)\To determine the nature of the soluble factor(s) required for allo-T cell activation. (3)\To determine whether surface Ia-antigen density is an important property in determining allostimulator potential or whether there might exist differences in accessibility of Ia antigenic determinants on MLR stimulator and non-stimulator Ia-positive B cells. (4)\To determine whether Ia-allostimulation can be defined in molecular terms by the use of a cell free stimulating system comprised of purified Ia antigens and soluble cytokines. (5)\To use purified Ia-antigen to isolate and characterize the T cell receptor for Ia-alloantigen. The elucidation of the recognition of and the response to allogeneic antigens of the I-region of the MHC may provide important insights relevant to the requirements for MHC-restricted antigen presentation as well as being important in its own right as providing information critical to an understanding of allograft rejection and transplantation immunity.